In 2009, Candida auris appeared seemingly out of nowhere.1 Since then, its rapid emergence in hospitals and extreme drug resistance has earned this pesky pathogen a spot on both the CDC and WHO high threat lists.2,3 Its success likely comes from its ability to persistently stick to surfaces, but how it does this was unclear. Recently, researchers discovered the clingy culprit, a new, uncharacterized protein, which they hope will inform new therapeutics.4 

Teresa O’Meara, a geneticist at the University of Michigan and author of the paper published in Science, started the investigation by probing the obvious offenders: 12 conserved adhesins, proteins that fungal pathogens use to stick to surfaces. “We really thought that one of these would be important,” said O’Meara. “It turns out that not really.” To expand their search, the researchers screened more than 2,000 C. auris mutants in search of one with limited clinging capacity. This led them to an unknown adhesin: Surface Colonization Factor 1 (Scf1). 

“What stands out is how strong the phenotypes are of this gene,” said Christina Cuomo, a fungal geneticist at Brown University who was not involved in the study. Although many adhesins are conserved across Candida species, Scf1 isn't, and only C. auris required Scf1 to stick to surfaces. 

O’Meara and her team discovered that, unlike other adhesins, the exposed N-terminal domain of Scf1 is enriched with cationic amino acids, which facilitate an incredibly strong bond— second only to covalent bonds—with certain surfaces. Mollusks and barnacles use a similar approach to cling tightly to rocks.

O’Meara’s team further demonstrated Scf1’s role in infections. C. auris strains lacking SCF1 exhibited reduced catheter and skin colonization in rodent and ex vivo human skin explant models, whereas overexpression of the gene drove this behavior. “What was really shocking to us was that it’s actually required for causing disease,” said O’Meara, who hopes to further probe the novel adhesin’s behaviors during infection in future experiments.

References 

  1. Satoh K, et al. Microbiol Immunol. 2009;53(1):41-44.
  2. CDC. Department of Health and Human Services, CDC. 2019. 
  3. WHO. World Health Organization. 2022.
  4. Santana DJ, et al. Science. 2023;381(6665):1461-1467.